Process for the preparation of thiazolic derivatives



United States Patent PROCESS FOR THE PREPARATION OF THIAZOLICDERIVATIVES Tullio Bacchetti, Milan, Itaiy, assignor to Carlo Erba S. p.A., Milan, Italy No Drawing. Application July 18, 1955, Serial No.522,845

6 Claims. Cl. 260306.7)

The present invention refers to the preparation of organic compounds ofthe general formula:

RIII C5 1 s where R is O, S or phenylimino, R' is phenyl, R" is loweralkyl and R is hydrogen or lower alkyl.

The new method of preparation is based on the reaction of ana-mercaptocarbonilic compound:

R"-COCH-SH with carbimidic compounds of the general formula:

RN=C=R in order to form the intermediate compounds:

R-NHC=R SCHOOR which, either by dry heating or in solution or else bymeans of drying agents lose a molecule of water forming the thiazolicderivatives:

The isolation of the intermediates is unnecessary since the reactiongives the thiazolic derivatives also directly.

This new method is of general use for all of the a. mercaptoketones andalso for the derivatives containing R" diflferent from those indicatedabove. It is particularly easy to work and gives very high yields(superior to 70% The new compounds thus obtained have shown in vitro tobe very active as anthelminthios and very little toxic: therapeutic useis foreseen.

Example 1 g. of mercaptoacetone are added to 13.2 g. of phenylisocyanateand heated for 6 hours at steam bath temperature.

By cooling the mixture gives a brown precipitate which is crystallizedfrom alcohol. It can contain variable quantities of diphenylurca formedthrough action of the water on phenylisocyanate. The product is thendissolved in benzene in which diphenylurea is little soluble, thesolution is filtrated and by concentration of the solvent about 16 g. of4-methyl-3-phenyl-thiazolone2 (white crystalline powder, M. 149-150 C.)are obtained.

Example 2 10 g. of 3-mercaptobutanone-2 and 12 g. of phenylisocyanateare heated for about 7 hours. The crystals can be separated andrecrystallized from alcohol. About 2,734,195 Patented Mar. 19 57 2 20 g.of 4,5-dimethyl-3-phenylthiazolone-2 (white crystalline powder, M. -102C.) are obtained.

Example 3 6 g. of l-mercaptobutanone-Z are added to 10.4 g. ofcarbodiphenylimide. The mixture is slowly heated up to 125 C. and thistemperature is maintained until, by cooling, a sample is solidified.Finally by crystallizin-g from alcohol about 10 g. of2-phenylimino-3-phenyl-4- ethyl-A4 thiaz-oline (white crystallinepowder, M. 115 C.) are obtained.

Example 4 One mole of 3-mercaptobutanone-2 is mixed with 1 mole ofphenylisothiocyanate and heated between 40 and 80 C. until crystalsstart separating. The mixture is cooled and then crystallized fromalcohol. The 3-phenyl- 4,S-dimethylthiazolthione-Z (yellow crystallinepowder, M. 103-104 C.) is obtained.

Example 5 According to the process described in Example 4,4-ethyl-3-phenylthiazolthione-2 (9 g. of white powder, M. -112 C.) canbe obtained from 6 g. of 1-mercaptobutanone-Z and 6.3 g. ofphenylisothiocyanate.

I claim: 1. Process for the preparation of thiazolic derivatives withanthelminthic action of the general formula:

Ell 1C R/// =R wherein R is selected from the group consisting of O, Sand phenylimino, R is phenyl, R" is lower alkyl and R" is selected fromthe group consisting of hydrogen and lower alkyl, characterized byreacting an u-mercaptocarbonilic compound of the general formula:

RCO-CH-SH RI! with carbimidic compounds of the general formula:

R--N=C=R 2. Process for the preparation of 4-methyl-3-phenylthiazolone-2CH3C-NCQH5 s characterized by reacting mercaptoacetone withphenylisocyanate.

3. Process for the preparation of 4,5-dimethyl-3-phenylthiazolone-Zcharacterized by reacting 3-mercaptobutanone-2 with phenylisocyanate.

4. Process for the preparation of 2-phenylimino-3- characterized byreacting 1-mercaptobutanone-2 with carbodiphenylimide.

5. Process for the preparation of 3-phenyl-4,5-dimethylthiazolthione-Z:

CH3C-NCOHs gh aggetex ized by regcgi ng 3-mercaptobutanone-2 withcharacterized by reacting l-mercaptobutanone z withphenylisothiocyanate. phenylisothiocyanate.

6. Process for the preparation of 4-ethyl 3-phenylthiazolthione-z;References Cited in-the file of this patent c n ofim-pma 5 Beilstein:Handbueh der Org. Chem, v01. 27, pp.

1. PROCESS FOR THE PREPARATION OF THIAZOLIC DERIVATIVES WITHANTHELMINTHIC ACTION OF THE GENERAL FORMULA: